The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: A clinical phase II study

Purpose: The aim of this phase II study was to evaluate the tumour response of neuroendocrine tumours to targeted irradiation with the radiolabelled somatostatin analogue 90Y-DOTATOC. In addition, the palliative effect of 90-Y-DO-TATOC treatment on the malignant carcinoid syndrome and tumour-associated pain was investigated. Patients and methods: Forty-one patients (mean age 53 years) with neuroendocrine gastroenteropancreatic and bronchial tumours were included. Eighty-two percent of the patients had therapy resistant and progressive disease. The treatment con sisted of four intravenous injections ofa total of 6000 MBq/m2 90Y-DOTATOC, administered at intervals of six weeks. Results:The overall response rate was 24%. For endocrine pancreatic tumours it was 36%. Complete remissions (CR) were found in 2% (1 of 41), partial remissions (PR) in 22% (9 of 41), minor response in 12% (5 of 41), stable disease (SD) in 49% (20 of4l) and progressive disease (PD) in 15% (6 of4l). The median follow up was 15 months (range 1 month to 36 months). The median duration of response has not been reached at 26 months. The two-year survival time was 76 ± 16%. Eighty-three percent of the patients suffering from the malignant carcinoid syndrome achieved a significant reduction of symptoms. The treatment was well tolerated. A reduction of pain score was observed in all patients (5 of 41) with morphine dependent tumour-associated pain. Side effects included grade LU (NCIGC) pancytopenia in 5%, and vomiting shortly after injection in 23%. No grade III—IV renal toxicity was observed. Conclusion: Targeted radiotherapy with 90Y-DOTATOC is a novel, well-tolerated treatment for neuroendocrine turnours with a remarkable objective response rate, survival time, and symptomatic respons

Opening up the Quantum Three-Box Problem with Undetectable Measurements

One of the most striking features of quantum mechanics is the profound effect exerted by measurements alone. Sophisticated quantum control is now available in several experimental systems, exposing discrepancies between quantum and classical mechanics whenever measurement induces disturbance of the interrogated system. In practice, such discrepancies may frequently be explained as the back-action required by quantum mechanics adding quantum noise to a classical signal. Here we implement the 'three-box' quantum game of Aharonov and Vaidman in which quantum measurements add no detectable noise to a classical signal, by utilising state-of-the-art control and measurement of the nitrogen vacancy centre in diamond. Quantum and classical mechanics then make contradictory predictions for the same experimental procedure, however classical observers cannot invoke measurement-induced disturbance to explain this discrepancy. We quantify the residual disturbance of our measurements and obtain data that rule out any classical model by > 7.8 standard deviations, allowing us for the first time to exclude the property of macroscopic state-definiteness from our system. Our experiment is then equivalent to a Kochen-Spekker test of quantum non-contextuality that successfully addresses the measurement detectability loophole

Origem e morfologia dos tanques naturais do Nordeste do Brasil

Natural tanks of Northeastern Brazil have been widely analyzed in paleontological terms. However, studies related to the origin and morphology of these natural depressions are stagnated since the 1990s. This work aims to present new interpretations about the origin of these tanks, as well as to establish an internationally correlated nomenclature and to propose a morphological classification of these features. Academic works elaborated from the beginning of the 19th century until more recent articles, including theses and dissertations, have been consulted on the application of the term, the paleontological importance and origin of the natural tanks in northeastern Brazil. We propose the use of the term natural tank (shallow and steeped) to depressions of non-fluvial origins on the bedrock, and maintain the term caldrons to those of fluvial origin. The previous models for the formation of natural tanks were based on three situations in subaerial environment. In this work, we associate the chemical corrosion and migration and concentration of charges in subsurface as important processes for the genesis of natural tanks. Instead of the necessity of the surface be exposed to start the formation of the cavity, the tank may have its origin and development associated with subedaphic environment.Os tanques naturais do Nordeste do Brasil têm sido amplamente analisados em termos paleontológicos. Entretanto, estudos relacionados à origem e morfologia dessas depressões naturais encontram-se estagnados desde a década de 1990. O presente trabalho tem como objetivo apresentar novas interpretações sobre a gênese desses tanques, bem como estabelecer uma nomenclatura correlacionável internacionalmente e propor uma classificação morfológica dessas feições. Foram consultados trabalhos acadêmicos elaborados desde o início do século XIX até artigos mais recentes, incluindo teses e dissertações, sobre a utilização do termo, a importância paleontológica e origem dos tanques naturais no nordeste brasileiro. Este trabalho propõe a utilização do termo tanque natural (raso e escarpado) para as cavidades naturais, de origens não-fluviais, sobre o embasamento cristalino, e manter o termo marmita, ou caldeirões, para aquelas de origem fluvial. Os modelos prévios para a origem dos tanques baseavam-se em três importantes situações, em ambiente subaéreo, para a formação dessas cavidades. Neste trabalho associa-se a corrosão química e a migração e concentração de cargas em subsuperfície como processos importantes para a gênese dos tanques naturais. Ao contrário da necessidade da superfície estar exposta para iniciar a formação da cavidade, o tanque pode ter sua origem e desenvolvimento associado ao ambiente subedáfico

Demonstration of entanglement-by-measurement of solid state qubits

Projective measurements are a powerful tool for manipulating quantum states. In particular, a set of qubits can be entangled by measurement of a joint property such as qubit parity. These joint measurements do not require a direct interaction between qubits and therefore provide a unique resource for quantum information processing with well-isolated qubits. Numerous schemes for entanglement-by-measurement of solid-state qubits have been proposed, but the demanding experimental requirements have so far hindered implementations. Here we realize a two-qubit parity measurement on nuclear spins in diamond by exploiting the electron spin of a nitrogen-vacancy center as readout ancilla. The measurement enables us to project the initially uncorrelated nuclear spins into maximally entangled states. By combining this entanglement with high-fidelity single-shot readout we demonstrate the first violation of Bells inequality with solid-state spins. These results open the door to a new class of experiments in which projective measurements are used to create, protect and manipulate entanglement between solid-state qubits.Comment: 6 pages, 4 figure

Online interventions to prevent mental health problems implemented in school settings: the perspectives from key stakeholders in Austria and Spain

Background: Schools are key settings for delivering mental illness prevention in adolescents. Data on stakeholders’ attitudes and factors relevant for the implementation of Internet-based prevention programmes are scarce. Methods: Stakeholders in the school setting from Austria and Spain were consulted. Potential facilitators (e.g. teachers and school psychologists) completed an online questionnaire (N=50), policy makers (e.g. representatives of the ministry of education and health professional associations) participated in semi-structured interviews (N=9) and pupils (N=29, 14–19 years) participated in focus groups. Thematic analysis was used to identify experiences with, attitudes and needs towards Internet-based prevention programmes, underserved groups, as well as barriers and facilitators for reach, adoption, implementation and maintenance. Results: Experiences with Internet-based prevention programmes were low across all stakeholder groups. Better reach of the target groups was seen as main advantage whereas lack of personal contact, privacy concerns, risk for misuse and potential stigmatization when implemented during school hours were regarded as disadvantages. Relevant needs towards Internet-based programmes involved attributes of the development process, general requirements for safety and performance, presentation of content, media/tools and contact options of online programmes. Positive attitudes of school staff, low effort for schools and compatibility to schools’ curriculum were seen as key factors for successful adoption and implementation. A sound implementation of the programme in the school routine and continued improvement could facilitate maintenance of online prevention initiatives in schools. Conclusions: Attitudes towards Internet-based mental illness prevention programmes in school settings are positive across all stakeholder groups. However, especially safety concerns have to be considered

Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper

<p>Abstract</p> <p>Background</p> <p>In animal studies tumor size is used to assess responses to anticancer therapy. Current standard for volumetric measurement of xenografted tumors is by external caliper, a method often affected by error. The aim of the present study was to evaluate if microCT gives more accurate and reproducible measures of tumor size in mice compared with caliper measurements. Furthermore, we evaluated the accuracy of tumor volume determined from ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET.</p> <p>Methods</p> <p>Subcutaneously implanted human breast adenocarcinoma cells in NMRI nude mice served as tumor model. Tumor volume (n = 20) was determined <it>in vivo </it>by external caliper, microCT and ¹⁸F-FDG-PET and subsequently reference volume was determined <it>ex vivo</it>. Intra-observer reproducibility of the microCT and caliper methods were determined by acquiring 10 repeated volume measurements. Volumes of a group of tumors (n = 10) were determined independently by two observers to assess inter-observer variation.</p> <p>Results</p> <p>Tumor volume measured by microCT, PET and caliper all correlated with reference volume. No significant bias of microCT measurements compared with the reference was found, whereas both PET and caliper had systematic bias compared to reference volume. Coefficients of variation for intra-observer variation were 7% and 14% for microCT and caliper measurements, respectively. Regression coefficients between observers were 0.97 for microCT and 0.91 for caliper measurements.</p> <p>Conclusion</p> <p>MicroCT was more accurate than both caliper and ¹⁸F-FDG-PET for <it>in vivo </it>volumetric measurements of subcutaneous tumors in mice.¹⁸F-FDG-PET was considered unsuitable for determination of tumor size. External caliper were inaccurate and encumbered with a significant and size dependent bias. MicroCT was also the most reproducible of the methods.</p

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Delocalized single-photon Dicke states and the Leggett- Garg inequality in solid state systems

We show how to realize a single-photon Dicke state in a large one-dimensional array of two- level systems, and discuss how to test its quantum properties. Realization of single-photon Dicke states relies on the cooperative nature of the interaction between a field reservoir and an array of two-level-emitters. The resulting dynamics of the delocalized state can display Rabi-like oscillations when the number of two-level emitters exceeds several hundred. In this case the large array of emitters is essentially behaving like a mirror-less cavity. We outline how this might be realized using a multiple-quantum-well structure and discuss how the quantum nature of these oscillations could be tested with the Leggett-Garg inequality and its extensions.Comment: 29 pages, 5 figures, journal pape